The goal of this project is to analyze by recombinant DNA techniques sequence transpositions and alterations in gene structure and expression which result from chemical and physical toxic/carcinogenic agents. Molecular clones of the "transposon-like" endogenous ecotropic viral genomes of BALB/c and RFM/Un mice have been constructed and characterized. Subgenomic regions have been subcloned to provide molecular probes to specifically detect the ecotropic provirus and any long terminal repeat (LTR) containing genetic regulatory elements. Detailed analysis of a large population of cloned genomes of the BALB/c endogenous retro-virus has revealed a significant variability in the U3 region of the LTR. These findings are intriguing due to the important multifunctional role of this region, including "transposon-like" integration and regulation of gene transcription. Ongoing and future studies involve the molecular cloning of reintegrated or transposed proviral genomes when identified in cultured and primary radiation induced myeloid leukemia cells. Analysis of alterations in gene expression due to the relocation of these elements will be performed using cloned DNA probes from adjacent cellular regions.